Following an extensive review by its board of directors, the Global HIV Vaccine Enterprise and its New York City-based Secretariat is streamlining its focus.

In a letter distributed Oct. 26, Jose Esparza, the interim president of the Enterprise’s Board of Directors, said the updated Enterprise would continue as an alliance of independent organizations dedicated to accelerating the development of AIDS vaccine candidates and would continue to focus on facilitating “mutual coordination, collaboration, knowledge sharing, and the optimization of resources and efforts in the field.”

But reflecting what Esparza described as a “leaner, more efficient” operation, the Enterprise will largely restrict its attention to three core functions that reflect these priorities. As it has done since 2007, the Enterprise’s Secretariat will continue to organize the annual AIDS Vaccine Conference. The Enterprise will also organize an annual Funders’ Forum to optimize use of current financial resources and hopefully attract new funding to the field. Finally, it will convene meetings on strategic issues where a collective effort is deemed most effective.

“The board is working very hard to rejuvenate the Enterprise with a model that is more agile, focused, streamlined, and relevant to the field,” says Esparza, senior advisor on vaccines for the Bill & Melinda Gates Foundation, who has served as interim president of the Enterprise board since late 2010, when Peter Piot, director of the London School of Hygiene & Tropical Medicine, resigned the post.

The genesis of the Global HIV Vaccine Enterprise occurred about a decade ago when a handful of leaders in the field of AIDS vaccine research began considering creating an organization that would bring greater coordination, collaboration, and transparency to the field. But there has always been a lack of consensus on how the Enterprise should be structured, what its role should be, and what kind of leader would best suit the organization’s needs, as well as those of the field (see The Enterprise Changes Course, IAVI Report, Sep.-Oct. 2011). These questions became even more apparent since Alan Bernstein, the first executive director of the Enterprise, resigned in June after three years at the helm.

Though Bernstein’s credentials included a background in research—he specialized in oncology and was founding president of the Canadian Institutes of Health Research—the Enterprise board may not necessarily select another scientist for the top slot, several Enterprise board members contend.

Along with a new executive director, the Enterprise Secretariat will also expand its board, which now has seven members, to comprise representatives of funders of research, advocacy groups, consortiums and institutions, global health organizations, governments and multilateral agencies, and industry partners. The new board will include approximately 15 members, says Mitchell Warren, executive director of the global advocacy organization AVAC and a member of the Enterprise board.

What isn’t likely to change is the Secretariat base of operations. Warren says the Enterprise will remain in New York City, where Bernstein established the Secretariat.

One program not explicitly defined in the Enterprise’s revised list of priorities and activities is its young and early career investigators (YECI) committee. The Enterprise created YECI in 2008 to address issues that posed challenges to the recruitment of young researchers into the HIV vaccine field. Warren says the concerns of young and early career investigators are still important and the board considers the work of YECI to be one of the great strengths of the Enterprise. “No one thinks we are going to step away from that,” he adds.

US Secretary of State Hillary Clinton, whose department oversees the President’s Emergency Plan for AIDS Relief (PEPFAR), laid out an ambitious goal of achieving an AIDS-free generation in a Nov. 8 address to the US National Institutes of Health. Clinton said prevention of mother-to-child transmission, expanding adult male circumcision programs, and more widespread treatment of HIV-infected individuals to curb transmission will all help pave the way to an AIDS-free generation.

According to an annual report released Nov. 21 by the Joint United Nations Programme on HIV/AIDS (UNAIDS), there is continued progress in battling AIDS, but achieving an AIDS-free generation remains a daunting task. UNAIDS estimates that 2.7 million people have become newly HIV infected each year for the last five years. The report noted that the number of new HIV infections occurring globally in 2010 dropped by more than 21% since 1997, when incidence peaked worldwide, which UNAIDS attributes primarily to behavioral changes including reductions in the numbers of sexual partners, increased condom use, and delayed age of first sex. In some countries, like Botswana, declines in incidence were also attributed to wider availability of antiretroviral (ARV) treatment. The number of people receiving treatment globally has steadily increased. Now, 6.6 million or 46% of the HIV-infected people in low- and middle-income countries eligible for treatment are receiving ARVs.

In sub-Saharan Africa, new cases declined by 26% since 1997, led by a 33% drop in South Africa, which continues to have the highest number of HIV-infected individuals. But from 2008 to 2010, there was an alarming 23% surge in the number of new HIV infections among adults and children in Eastern Europe and Central Asia, helping keep the global number of new infections steady.

What are the risks and benefits of using hormonal contraception in HIV prevention trials?

Because little or no human data exist regarding safety of HIV vaccine candidates during pregnancy, either for the woman or the fetus, investigators usually require women of reproductive age to use contraception when they decide to participate in AIDS vaccine trials. Pregnant or breast-feeding women are excluded from participating in HIV vaccine trials.

If women choose to volunteer for an HIV vaccine trial, the nurses and staff at clinical trial centers go to great lengths to deliver pregnancy prevention counseling before the study begins, and to provide women with different contraception options, such as male or female condoms, oral hormonal contraceptives that must be taken daily, or injectable hormonal contraceptives such as Depo-Provera, which lasts for three months.

Injectable hormonal contraception is the most popular among women in developing countries, where the burden of HIV/AIDS is highest and the need for an AIDS vaccine is greatest. In sub-Saharan Africa, for instance, about 12 million women use injectable contraceptives, 8 million use oral contraceptives, and another 11 million use condoms, according to the Alan Guttmacher Institute, a New York City-based non-profit that advances sexual and reproductive health research. About 140 million women worldwide use hormonal contraceptives. Injectable contraceptives have the clear advantage of lasting for three months. All of the other methods are behavior dependent. This makes injectable contraception a preferable method.

However, a number of studies have suggested that the use of hormonal contraception may increase a woman’s risk of HIV acquisition. The most recent and strongest findings appeared in the October 18issue of the scientific journalLancet InfectiousDiseases, in which researchers from the University of Washington reported a doubling of the risk of HIV infection among women and, for the first time, a doubling of the risk of HIV transmission from women to men.

While the study did not differentiate between oral or injectable hormonal contraceptives, the long-acting injectable hormonal contraceptives were the most commonly used by women in the study, involving 3,790 heterosexual serodiscordant couples—in which one partner is HIV infected and the other is not. The cohort of serodiscordant couples was enrolled in Botswana, Kenya, Rwanda, South Africa, Tanzania, Uganda, and Zambia, and is the largest group in which the effect of hormonal contraception on HIV transmission has been studied.

The mechanism

Despite the recent data, the mechanism of how hormonal contraception increases the risk of HIV infection is not entirely clear. Hormonal contraceptives primarily work by suppressing the release of protein hormones that regulate reproductive development, which in turn prevents the ovary from releasing eggs and deprives sperm of their targets.

Some hormonal contraceptives, such as birth control pills, contain small amounts of synthetic reproductive hormones from both the estrogen and progestin families. Others, such as Depo-Provera, contain only progestin.

Hormonal contraceptives that contain just progestin also appear to be able to cause the cervical mucus to thicken, which blocks and prevents sperm from fertilizing an egg. And progestin-only hormonal contraception also thins the lining of the uterus, which in theory could prevent pregnancy by keeping a fertilized egg from attaching to the uterus.

An animal model

Scientists have been studying the effects of hormonal contraception in nonhuman primates. The vaginal mucosa is a common portal of entry for both HIV and simian immunodeficiency virus (SIV), the monkey equivalent of HIV, and identifying the mechanisms that accelerate or block viral entry in this region is important both in the study of HIV pathogenesis and prevention.

By labeling HIV with a fluorescent protein that causes the pathogen to light up like a neon sign, scientists were able to track viral particles within the vaginal mucosa of monkeys, some of which had been given the hormonal contraceptive Depo-Provera. Scientists observed more T cells—the primary targets of HIV—close to the mucosal surfaces of monkeys treated with Depo-Provera. This might explain why the use of the hormonal contraceptive increases HIV transmission.

While researchers continue to study how reproductive hormones may or may not influence HIV transmission and infection, it is likely that women will still be offered multiple contraception options, including hormonal contraceptives, if they are enrolled in HIV vaccine and other prevention trials.

However, some caution may be warranted in the future. The World Health Organization is convening a meeting in January to consider whether the evidence suggesting hormonal contraception increases HIV infection and/or transmission risk is now strong enough for them to issue a warning. Still, researchers who conducted the most recent study expect hormonal contraception will continue to be offered in HIV prevention trials.